Family planning clinics that leave the US government’s Title X programme may have to return or destroy any contraceptives they bought at a discount rate.1Many clinics throughout the US are currently…
Ready. Set. Move! Sports Medicine Australia advocates movement as medicine for all!
Ageing, death and taxes are certain: can physical activity (PA) help us age more gracefully? While we cannot help you with taxes, we are certain that this issue is packed with important new evidence on various less explored aspects of
Dolutegravir plus Two Different Prodrugs of Tenofovir to Treat HIV
A first-line regimen of tenofovir disoproxil fumarate (TDF) with either lamivudine (3TC) or emtricitabine (FTC) plus efavirenz (EFV) for the treatment of human immunodeficiency virus infection (HIV) is recommended by the World Health Organization (WHO) because it can be safely
Class-Switch Recombination Occurs Infrequently in Germinal Centers
Germinal centers (GCs) have long been considered sites in which Ig class-switch recombination (CSR) is favored. Roco et al. show that CSR occurs during the initial T cell:B cell interaction prior to GC formation and rapidly declines as B cells differentiate into
Multidisciplinary transcatheter aortic valve replacement heart team programme improves mortality in aortic stenosis
Objectives To analyse the effect of the implementation of a transcatheter aortic valve replacement (TAVR) and multidisciplinary heart team programme on mortality in severe aortic stenosis (AS). Methods A retrospective, observational cohort study was performed using the echocardiography, cardiothoracic surgery
Development of a Chimeric Model to Study and Manipulate Human Microglia In Vivo
Hasselmann, Coburn, et al. validate a new xenotransplantation paradigm to study iPSC-derived human microglia in vivo. This chimeric approach rectifies many of the deficits observed in culture models, providing new insight into the functional and transcriptional responses of human microglia to inflammatory
Marcel Waldinger: neuropsychiatrist and researcher who defined premature ejaculation
bmj;366/jul30_9/l4940/FAF1faThe cover of the 1997 doctoral thesis of Dutch neuropsychiatrist and sexual medicine researcher Marcel Waldinger features a stopwatch.1 Through such low tech means,…
Brachytherapy: An overview for clinicians
Abstract Brachytherapy is a specific form of radiotherapy consisting of the precise placement of radioactive sources directly into or next to the tumor. This technique is indicated for patients affected by various types of cancers. It is an optimal tool
[Editorial] Asbestos exposure: the dust cloud lingers
Exposure to asbestos fibres is to blame for most (>80%) cases of the notoriously incurable cancer, malignant mesothelioma. The UK death toll from asbestos-related mesothelioma is now reaching its peak, according to figures released by the Health and Safety Executive.
Global HIV Treatment — Turning Headwinds to Tailwinds
We perhaps naively thought that the issue of which antiretroviral therapy (ART) to offer 38 million persons living with human immunodeficiency virus (HIV) worldwide was settled for now. Integrase inhibitors had a better side-effect profile and were more potent than
Functional dissection of the Sox9–Kcnj2 locus identifies nonessential and instructive roles of TAD architecture
Nature Genetics, Published online: 29 July 2019; doi:10.1038/s41588-019-0466-z Removal of boundary and intra-TAD CTCF-binding sites at the Sox9–Kcnj2 locus in mice leads to TAD fusion but no major changes in gene expression. Gene misexpression and disease phenotypes were obtained through
DNA sensing by the cGAS–STING pathway in health and disease
Nature Reviews Genetics, Published online: 29 July 2019; doi:10.1038/s41576-019-0151-1 The cGAS–STING pathway forms a major DNA-sensing mechanism in mammalian cells. This Review summarizes the current knowledge of cGAS–STING signalling and regulation, highlighting emerging evidence of its role in monogenic inflammatory
Case 23-2019: A 52-Year-Old Man with Fever, Cough, and Hypoxemia
Presentation of Case. Dr. Lila M. Martin (Medicine): A 52-year-old man was transferred to this hospital for evaluation and treatment of hypoxemia. The patient had been in his usual state of health until 7 days before transfer to this hospital,
[Editorial] Are 2 million bottles of PrEP an empty gesture?
That a drug does not work if patients do not take it, is a familiar phrase to those working in HIV, usually applied to treatment adherence. But the stalling decline in HIV incidence in the USA shows that the same
Precise Long-Range Microcircuit-to-Microcircuit Communication Connects the Frontal and Sensory Cortices in the Mammalian Brain
Ren et al. identify presynaptic neurons innervating individual excitatory neuron clones that constitute microcircuits in the sensory cortex and reveal that input neurons in the frontal cortex are organized in discrete vertical clusters and preferentially form synapses with each other.
Case 23-2019: A 52-Year-Old Man with Fever, Cough, and Hypoxemia
Presentation of Case. Dr. Lila M. Martin (Medicine): A 52-year-old man was transferred to this hospital for evaluation and treatment of hypoxemia. The patient had been in his usual state of health until 7 days before transfer to this hospital,
John Kenneth Roberts
bmj;366/jul29_13/l4900/FAF1faJohn Kenneth Roberts (“Ken”) was born in a humble terraced house in Holyhead. His father was on the footplate of the LMS locomotives, including the Irish Mail. At the…
Highlights from this issue
Diagnostic uncertainty and physician experience We commonly use chest x-ray (CXR) to diagnose community-acquired pneumonia (CAP) in the Emergency Department. The 2015 ESCAPED study found that in patients without parenchymal infiltrates on CXR, routine thoracic CT scan was positive for
Overall Survival with Ribociclib plus Endocrine Therapy in Breast Cancer
Although breast cancer is known to be more aggressive and to be associated with a poorer prognosis in younger women than in older women, the recommended treatment for hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer
Comorbid chronic diseases and cancer diagnosis: disease-specific effects and underlying mechanisms
Nature Reviews Clinical Oncology, Published online: 26 July 2019; doi:10.1038/s41571-019-0249-6 The majority of patients with cancer have at least one chronic health condition at the time of diagnosis. Nonetheless, how such conditions influence the timeliness of diagnosis remains largely unknown.
Dolutegravir plus Two Different Prodrugs of Tenofovir to Treat HIV
A first-line regimen of tenofovir disoproxil fumarate (TDF) with either lamivudine (3TC) or emtricitabine (FTC) plus efavirenz (EFV) for the treatment of human immunodeficiency virus infection (HIV) is recommended by the World Health Organization (WHO) because it can be safely
Heartbeat: blood pressure and left ventricular remodelling in young athletes
Pre-participation screening of athletes mostly has focused on identifying those at increased risk of sudden cardiac death. However, screening also offers an opportunity for primary prevention of cardiovascular disease. In a large cohort of young (age 13–35 years) athletes, Hedman
Vijyarangam Senthilkumar Shanmugam
bmj;366/jul26_10/l4883/FAF1faVijyarangam Senthilkumar Shanmugam (“Kumar”) was an incredible, brave, and sincere doctor. He completed his medical training in 2000, graduating from Madurai Medical…
Contribution of spurious transcription to intellectual disability disorders
During the development of multicellular organisms, chromatin-modifying enzymes orchestrate the establishment of gene expression programmes that characterise each differentiated cell type. These enzymes also contribute to the maintenance of cell type-specific transcription profiles throughout life. But what happens when epigenomic
Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer
Metastatic pancreatic cancer is particularly refractory to treatment. Current standard-of-care first-line treatments are associated with a median progression-free survival of approximately 6 months, and fewer than 10% of patients are alive 5 years after the initial diagnosis. Loss-of-function…
Obstetric Care Consensus, Number 9: Levels of Maternal Care
Maternal mortality and severe maternal morbidity, particularly among women of color, have increased in the United States. The leading medical causes of maternal mortality include cardiovascular disease, infection, and common obstetric complications such as hemorrhage and vary by timing relative
Neuropeptide CGRP Limits Group 2 Innate Lymphoid Cell Responses and Constrains Type 2 Inflammation
Neuronal and immune systems coordinately orchestrate responses at mucosal barriers. Nagashima et al. applied scRNA-seq technology to track type 2 immune responses in worm infection, identifying neuropeptide CGRP as a factor that modulates inflammation. The study suggests that CGRP may be
Case 23-2019: A 52-Year-Old Man with Fever, Cough, and Hypoxemia
Presentation of Case. Dr. Lila M. Martin (Medicine): A 52-year-old man was transferred to this hospital for evaluation and treatment of hypoxemia. The patient had been in his usual state of health until 7 days before transfer to this hospital,
A Multicenter Trial of Vena Cava Filters in Severely Injured Patients
Venous thromboembolism is common after major trauma. A prospective surveillance study involving 349 consecutive severely injured patients showed that without prophylactic anticoagulation, proximal deep-vein thrombosis occurred in 18% of patients, and pulmonary embolism occurred in 11%. More…
Targeting Pathogenic Lafora Bodies in Lafora Disease Using an Antibody-Enzyme Fusion
Lafora disease (LD) is a devastating childhood epilepsy caused by intracellular, aberrant glycogen aggregates called Lafora bodies (LBs) in the brain and other tissues. Herein, Brewer et al. generated a first-in-class antibody-enzyme fusion, VAL-0417, that degrades LBs in vitro and in vivo in
Bad to the Bone
A 52-year-old man presented to the emergency department with nausea, vomiting, and profound lethargy. He had noted mild nausea and fatigue for approximately 5 months. Given acute worsening of his symptoms in the days leading up to presentation, he sought
Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer
Metastatic pancreatic cancer is particularly refractory to treatment. Current standard-of-care first-line treatments are associated with a median progression-free survival of approximately 6 months, and fewer than 10% of patients are alive 5 years after the initial diagnosis. Loss-of-function…
Postacute Care — The Piggy Bank for Savings in Alternative Payment Models?
After many years under siege, the edifice of fee-for-service payment is beginning to crumble. Federal, state, and private payers are approaching a tipping point when it comes to implementation of global and episode-based payment models for hospitals. According to the
The Opportunity of CBD — Reforming the Law
Over the past year, dietary supplements and foods containing cannabidiol (CBD) have swept into retail establishments and onto the Internet, with estimated annual U.S. sales now exceeding $200 million and growing rapidly. Recently, however, the Food and Drug Administration (FDA)
Measles
Foreword. This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors’ clinical recommendations. Stage.
Implementation Science for the Bedside
Early in the morning, my intern told the patient that his kidneys had quit working, that he was in danger from electrolyte derangements, and that dialysis could save his life. In the 24 hours since his admission to the hospital,
Cortical Neurogenesis Requires Bcl6-Mediated Transcriptional Repression of Multiple Self-Renewal-Promoting Extrinsic Pathways
Bonnefont et al. show that Bcl6 promotes neurogenesis by directly repressing genes belonging to the major signaling pathways promoting cortical progenitor self-renewal. These data indicate that a single cell-intrinsic factor represses multiple extrinsic signaling pathways to ensure irreversible neurogenic commitment.
Measles
Foreword. This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors’ clinical recommendations. Stage.
Resting-State Structure and Gating Mechanism of a Voltage-Gated Sodium Channel
An engineered bacterial NaV channel adopts a resting conformation in the absence of a membrane potential, enabling structural analysis and elucidation of the full voltage-dependent gating mechanism.
[Editorial] Prioritising primary care in the USA
Although the USA spends more on health care despite having worse outcomes than other high-income nations, one area where it underinvests is primary care. Research has shown that higher levels of spending on primary care lead to improved patient outcomes
A Multicenter Trial of Vena Cava Filters in Severely Injured Patients
Venous thromboembolism is common after major trauma. A prospective surveillance study involving 349 consecutive severely injured patients showed that without prophylactic anticoagulation, proximal deep-vein thrombosis occurred in 18% of patients, and pulmonary embolism occurred in 11%. More…
New PM promises faster GP appointments and hospital upgrades
Patients should get quicker access to GP appointments, and hospitals will receive “upgrades,” as part of plans laid out by the new prime minister, Boris Johnson, who took over the post on 24…
Highlights from this issue
Altered retinoid metabolism gene expression in chronic Stevens-Johnson’s syndrome (see page 1015) Altered vitamin A metabolism in chronic ocular sequelae of SJS. Photophobia and sensations of dryness in migraine patients occur independent of baseline tear volume and improve following botulinum
PERSEPHONE — implications for clinical practice in 2019
Nature Reviews Clinical Oncology, Published online: 24 July 2019; doi:10.1038/s41571-019-0256-7 Five randomized trials have been conducted to prove that shorter duration of trastuzumab treatment (9 weeks or 6 months) can replace the standard duration (1 year). The results of PERSEPHONE,
Maintenance Therapy in Metastatic Solid Tumors: Innovative Strategy or Simple Second-line Treatment?
Managing metastatic diseases involves defining the best strategy that is supposed to take into account both efficacy and quality of life. To this end, clinicians use stop and go or maintenance strategies. As a matter of fact, 2 maintenance strategies
Combating EPA Rollbacks — Health Care’s Response to a Retreat on Climate
The world’s climate crisis has spared no one. Science tells us that the harms of climate change will worsen with time if we fail to take substantial actions now to reduce carbon pollution. In the United States, the growing burden
Global HIV Treatment — Turning Headwinds to Tailwinds
We perhaps naively thought that the issue of which antiretroviral therapy (ART) to offer 38 million persons living with human immunodeficiency virus (HIV) worldwide was settled for now. Integrase inhibitors had a better side-effect profile and were more potent than
Should women with gestational diabetes be screened at delivery hospitalization for type-2 diabetes?
Less than half of women with gestational diabetes mellitus (GDM) are screened for type 2 diabetes (DM) postpartum (PP). Other approaches to postpartum screening need to be evaluated including the role of screening during the delivery hospitalization
RNA sequencing: the teenage years
Nature Reviews Genetics, Published online: 24 July 2019; doi:10.1038/s41576-019-0150-2 This Review discusses advances in RNA-sequencing technologies and methods over the past decade and outlines adaptations that are enabling a fuller understanding of RNA biology, from when and where an RNA
Combating EPA Rollbacks — Health Care’s Response to a Retreat on Climate
The world’s climate crisis has spared no one. Science tells us that the harms of climate change will worsen with time if we fail to take substantial actions now to reduce carbon pollution. In the United States, the growing burden
Combating EPA Rollbacks — Health Care’s Response to a Retreat on Climate
The world’s climate crisis has spared no one. Science tells us that the harms of climate change will worsen with time if we fail to take substantial actions now to reduce carbon pollution. In the United States, the growing burden
The Cholinergic Basal Forebrain Links Auditory Stimuli with Delayed Reinforcement to Support Learning
Sensory stimuli and behavioral reinforcement can be separated by long silent intervals. Guo et al. characterize a distributed neural circuit in the mouse forebrain that supports auditory fear learning by linking brief sounds with aversive events that occur many seconds later.
Combating EPA Rollbacks — Health Care’s Response to a Retreat on Climate
The world’s climate crisis has spared no one. Science tells us that the harms of climate change will worsen with time if we fail to take substantial actions now to reduce carbon pollution. In the United States, the growing burden
Combating EPA Rollbacks — Health Care’s Response to a Retreat on Climate
The world’s climate crisis has spared no one. Science tells us that the harms of climate change will worsen with time if we fail to take substantial actions now to reduce carbon pollution. In the United States, the growing burden
[Editorial] Rinderpest, smallpox, and the imperative of destruction
In June, The Pirbright Institute (UK) announced that it had destroyed its final archived stocks of rinderpest, the devastating viral disease of cattle that was declared eradicated in 2011. Rinderpest is only the second infection to be eradicated from the
Dolutegravir-Based or Low-Dose Efavirenz–Based Regimen for the Treatment of HIV-1
Until mid-2018, the preferred initial antiretroviral therapy (ART) recommended in the World Health Organization (WHO) guidelines for human immunodeficiency virus type 1 (HIV-1) infection consisted of two nucleoside reverse-transcriptase inhibitors (NRTIs) combined with a nonnucleoside…
Health Care Autonomy of Women Living with HIV
In sub-Saharan Africa, more than 60% of all adults living with HIV in 2018 were women, according to the Joint United Nations Programme on HIV and AIDS (https://aidsinfo.unaids.org). Largely as a result of early access to HIV testing and antiretroviral
Combating EPA Rollbacks — Health Care’s Response to a Retreat on Climate
The world’s climate crisis has spared no one. Science tells us that the harms of climate change will worsen with time if we fail to take substantial actions now to reduce carbon pollution. In the United States, the growing burden
Combating EPA Rollbacks — Health Care’s Response to a Retreat on Climate
The world’s climate crisis has spared no one. Science tells us that the harms of climate change will worsen with time if we fail to take substantial actions now to reduce carbon pollution. In the United States, the growing burden
Asthma: assess all patients for future attack risk and tailor care accordingly, new guideline advises
All patients with asthma should have their risk of having a future attack assessed and have their monitoring, treatment, and care tailored accordingly, new guidelines from the British Thoracic…
Tools to facilitate communication during physician‐patient consultations in cancer care: An overview of systematic reviews
Abstract Tools have been developed to facilitate communication and support information exchange between people diagnosed with cancer and their physicians. Patient‐reported outcome measures, question prompt lists, patient‐held records, tape recordings of consultations, decision aids, and survivorship care plans have all
[Editorial] The value of affordable care
The long-overlooked issue in the USA of leaving drug pricing entirely to market competition, which results in higher drug costs in this country than others where governments directly or indirectly regulate prices, seems to finally be getting the attention it
Neural-Tube Defects and Antiretroviral Treatment Regimens in Botswana
Neural-tube defects occur by the end of the sixth week of pregnancy (i.e. the fourth week after fertilization) and have been associated with exposure to specific drugs early in pregnancy. Concerns about neural-tube defects among children exposed to efavirenz at
Activation Dynamics and Immunoglobulin Evolution of Pre-existing and Newly Generated Human Memory B cell Responses to Influenza Hemagglutinin
Influenza vaccination occurs in the context of pre-existing immunity. Andrews et al. compare the pre-existing memory IgG B cell response recognizing conserved epitopes on influenza hemagglutinin with the newly generated response to strain-specific epitopes upon H7N9 vaccination. The differences in magnitude,
Health Care Spending, Utilization, and Quality 8 Years into Global Payment
The reform of health care payment systems has centered on moving providers away from fee-for-service payment. The most clinically comprehensive of the alternative payment models — population-based global payment — gives providers a spending target or budget for the entire
Neural-Tube Defects and Antiretroviral Treatment Regimens in Botswana
Neural-tube defects occur by the end of the sixth week of pregnancy (i.e. the fourth week after fertilization) and have been associated with exposure to specific drugs early in pregnancy. Concerns about neural-tube defects among children exposed to efavirenz at
How mRNA Localization and Protein Synthesis Sites Influence Dendritic Protein Distribution and Dynamics
A steady protein supply is critical to synaptic function. Here, Fonkeu et al. present a theoretical framework, validated by experimental data, that details how local and dendritic mRNAs shape dendritic protein dynamics across short and long timescales.
[Editorial] Fetal tissue research: focus on the science and not the politics
The use of human fetal tissue and embryonic stem cells in medicine and research has led to many advances through an improved understanding of congenital abnormalities and human disease development. This research has enabled the use of stem cells lines
Breast Milk for Preemies
Although 83.9% of all US infants receive breast milk within the first few days of life, this rate is about 7% to 13% lower among premature infants despite the many benefits of breast milk, a CDC report found.
Locally adapted QOF led to improvements in patient care for long term conditions
The introduction of a local Quality and Outcomes Framework (QOF) alternative in Somerset led to more patient centred care and increased multidisciplinary team working, a new study has found.1By…
One step closer to personalised prescribing of antidepressants: using real-world data together with patients and clinicians’ preferences
Antidepressants for many decades have been shown to be an effective treatment for depressive disorder.1 Approximately 80% of people with depressive disorder in the UK will have been prescribed an antidepressant within the first year following diagnosis.2 Indeed, about 71
Susceptible loci associated with autoimmune disease as potential biomarkers for checkpoint inhibitor-induced immune-related adverse events
Unprecedented successes regarding cancer immunotherapy have been achieved, in which therapeutic agents are used to target immune cells rather than cancer cells. The most effective immunotherapy to date is the group of immune checkpoint inhibitors (CPI), targeting, for example, cytotoxic
PARP inhibition — opportunities in pancreatic cancer
Nature Reviews Clinical Oncology, Published online: 22 July 2019; doi:10.1038/s41571-019-0257-6 An urgent clinical need exists to improve the survival of patients with pancreatic cancer through biomarker-driven therapeutic strategies. Such approaches include the targeting of metastatic pancreatic cancer that harbours germline
Dolutegravir Use at Conception — Additional Surveillance Data from Botswana
To the Editor: In May 2018, an unscheduled analysis from the Botswana–Harvard AIDS Institute Partnership Tsepamo birth-outcomes surveillance study showed a higher prevalence of neural-tube defects among infants born to women who were using dolutegravir-based antiretroviral treatment (ART) regimens…
The effect of placental location in cases of placenta accreta spectrum
Placenta accreta spectrum (PAS) affects approximately 3:1000 pregnancies. There is a paucity of data evaluating the effect of placental location on diagnosis, risk factors, and resultant outcomes in cases of PAS.
Reply to ‘Inflated performance measures in enhancer–promoter interaction-prediction methods’
Nature Genetics, Published online: 22 July 2019; doi:10.1038/s41588-019-0452-5 Reply to ‘Inflated performance measures in enhancer–promoter interaction-prediction methods’
Caseload management and outcome of patients with aortic stenosis in primary/secondary versus tertiary care settings–design of the IMPULSE enhanced registry
Background Severe aortic stenosis (AS) is one of the most common and most serious valve diseases. Without timely intervention with surgical aortic valve replacement or transcatheter aortic valve replacement, patients have an estimated survival of 2–3 years. Guidelines for the
Dolutegravir Use at Conception — Additional Surveillance Data from Botswana
To the Editor: In May 2018, an unscheduled analysis from the Botswana–Harvard AIDS Institute Partnership Tsepamo birth-outcomes surveillance study showed a higher prevalence of neural-tube defects among infants born to women who were using dolutegravir-based antiretroviral treatment (ART) regimens…
Neural Organization of Hierarchical Motor Sequence Representations in the Human Neocortex
Hierarchical movement sequences are often assumed to mirror an anatomical hierarchy of brain regions. Using representational fMRI analysis, Yokoi and Diedrichsen challenge this common assumption. Although the primary motor cortex represents elementary movements, chunk and sequence representations coexist in the
Neural-Tube Defects and Antiretroviral Treatment Regimens in Botswana
Neural-tube defects occur by the end of the sixth week of pregnancy (i.e. the fourth week after fertilization) and have been associated with exposure to specific drugs early in pregnancy. Concerns about neural-tube defects among children exposed to efavirenz at
NHS is spending more on private providers despite government pledges
The NHS in England is spending increasing amounts of money in the private sector to provide services for its patients despite government promises to roll back on the role of the independent sector in…
Speech databases for mental disorders: A systematic review
Background The employment of clinical databases in the study of mental disorders is essential to the diagnosis and treatment of patients with mental illness. While text corpora obtain merely limited information of content, speech corpora capture tones, emotions, rhythms and
The heart and the brain: cardiovascular risk factors, atrial fibrillation, and dementia
Case 22-2019: A 65-Year-Old Woman with Weakness, Dark Urine, and Dysphagia
Presentation of Case. Dr. Doll L. Golden (Medicine): A 65-year-old woman was admitted to this hospital because of falls, weakness, dark urine, and difficulty swallowing. Approximately 35 years before the current admission, the patient underwent staged male-to-female sex reassignment surgery
Case 22-2019: A 65-Year-Old Woman with Weakness, Dark Urine, and Dysphagia
Presentation of Case. Dr. Doll L. Golden (Medicine): A 65-year-old woman was admitted to this hospital because of falls, weakness, dark urine, and difficulty swallowing. Approximately 35 years before the current admission, the patient underwent staged male-to-female sex reassignment surgery
Maternal surgery during pregnancy has a transient adverse effect on the developing fetal rabbit brain
Recently the US Food and Drug Administration called for cautious use of anesthetic drugs during pregnancy. In 0.2-2% of pregnancies non-obstetric surgery is being performed. The consequences of anesthesia during pregnancy on fetal development remain unclear and preclinical studies in
Microenvironment plasticity confers cetuximab resistance
Nature Reviews Clinical Oncology, Published online: 19 July 2019; doi:10.1038/s41571-019-0259-4 Microenvironment plasticity confers cetuximab resistance
Author Correction: Atlas of group A streptococcal vaccine candidates compiled using large-scale comparative genomics
Nature Genetics, Published online: 19 July 2019; doi:10.1038/s41588-019-0482-z Author Correction: Atlas of group A streptococcal vaccine candidates compiled using large-scale comparative genomics
Effect of Systolic and Diastolic Blood Pressure on Cardiovascular Outcomes
Thresholds for hypertension and prevailing concepts about hypertension have shifted over time. Constructs about the consequences of isolated diastolic, isolated systolic, and combined systolic and diastolic hypertension evolved in the 1960s, with a prevailing notion that only diastolic hypertension…
Case 22-2019: A 65-Year-Old Woman with Weakness, Dark Urine, and Dysphagia
Presentation of Case. Dr. Doll L. Golden (Medicine): A 65-year-old woman was admitted to this hospital because of falls, weakness, dark urine, and difficulty swallowing. Approximately 35 years before the current admission, the patient underwent staged male-to-female sex reassignment surgery
Drug-Induced Liver Injury — Types and Phenotypes
Drug-induced liver injury is an uncommon but challenging clinical problem with respect to both diagnosis and management. Its incidence is estimated to be 14 to 19 cases per 100,000 persons, with jaundice accompanying 30% of cases. Drug-induced liver injury is
Drug-Induced Liver Injury — Types and Phenotypes
Drug-induced liver injury is an uncommon but challenging clinical problem with respect to both diagnosis and management. Its incidence is estimated to be 14 to 19 cases per 100,000 persons, with jaundice accompanying 30% of cases. Drug-induced liver injury is
HIV Testing and Treatment with the Use of a Community Health Approach in Rural Africa
Antiretroviral therapy (ART) has the dual benefit of improving the health of individual persons and of reducing transmission of human immunodeficiency virus (HIV) infection. With 1.8 million new HIV infections and 1.0 million deaths annually, it is clear that the
Effect of Systolic and Diastolic Blood Pressure on Cardiovascular Outcomes
Thresholds for hypertension and prevailing concepts about hypertension have shifted over time. Constructs about the consequences of isolated diastolic, isolated systolic, and combined systolic and diastolic hypertension evolved in the 1960s, with a prevailing notion that only diastolic hypertension…
The Right and Left Hands of the State — Two Patients at Risk of Deportation
Case A: London. Twenty-year-old Ms. Z. presented to the emergency department (ED) of a hospital in London, anxious and hyperventilating after 4 days sheltering on night buses. She was brought in by an elderly couple whom she had approached when
Case 22-2019: A 65-Year-Old Woman with Weakness, Dark Urine, and Dysphagia
Presentation of Case. Dr. Doll L. Golden (Medicine): A 65-year-old woman was admitted to this hospital because of falls, weakness, dark urine, and difficulty swallowing. Approximately 35 years before the current admission, the patient underwent staged male-to-female sex reassignment surgery
The impact of editorial policy
Editorials throughout 2018 made explicit the journal’s editorial direction. In particular, we drew readers’ attention to the process of manuscript selection1 and the purpose selection was aiming to achieve.2 Rather than being a passive filtering process, editorial selection aims to
Highlights from this issue
Global health: Charges to migrant children’s families In a hard-hitting salvo, Russell and colleagues argue that recent changes to charging regulations in the NHS, both undermine child health and represent a departure from the founding principles of the organisation. The
Planned Parenthood president forced out as organisation faces US government funding cuts
The president and chief executive of Planned Parenthood, Leana Wen, left her job on Tuesday over “philosophical differences” about the organisation’s direction. Wen, the former health commissioner of…
Cancer medicines in Asia and Asia-Pacific: What is available, and is it effective enough?
This review article is an overview of the session at the European Society for Medical Oncology (ESMO) Asia 2018 Congress entitled: ‘Cancer medicines in Asia and Asia-Pacific: What is available, and is it effective enough?’. The article provides an overview
Outcompeting p53-Mutant Cells in the Normal Esophagus by Redox Manipulation
Normal human esophagus contains p53 mutant progenitors. Fernandez-Antoran and colleagues show that p53 mutant progenitors outcompete their wild-type neighbors after low-dose ionizing radiation. This effect is reversed by antioxidant pretreatment. p53 mutant cells can be displaced from normal tissues via
The Polycomb Repressor Complex 1 Drives Double-Negative Prostate Cancer Metastasis by Coordinating Stemness and Immune Suppression
Su et al. show that PRC1 drives metastasis of androgen receptor and neuroendocrine double-negative prostate cancers by regulating CCL2 expression. CCL2 governs self-renewal and recruitment of TAM and Treg. PRC1 inhibition combined with immune checkpoint blockade reverses these processes and suppresses
Mucosal Neuromas
Figure 1.
Controlling CRISPR-Cas9 Gene Editing
RNA genetic medicines, in both development and clinical use, are highly selective therapeutics that recognize their cognate target DNA or RNA by base pairing. These medicines include CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats–Cas9 endonuclease), an experimental medicine…
Tofacitinib in Amyopathic Dermatomyositis–Associated Interstitial Lung Disease
To the Editor: Anti–melanoma differentiation–associated protein (MDA) 5 (anti-MDA5)–positive amyopathic dermatomyositis (ADM)–associated interstitial lung disease (ILD) (hereafter, ADM-ILD) is a rapidly progressive and life-threatening disease. Despite aggressive conventional treatments with…
Correction: Fractional flow reserve derived from microcatheters versus standard pressure wires: a stenosis-level meta-analysis
Sodium-Intake Reduction and the Food Industry
A recent report from the National Academies of Sciences, Engineering, and Medicine (NASEM) on dietary sodium intake adds overwhelming weight to the already strong imperative to reduce the amount of sodium in the U.S. food supply. Some food companies had
A “Never Event” That Could Kill Millions
During my residency in emergency medicine, an attending physician watching me place a central venous catheter spoke up. “Don’t let go of the wire!” he warned. “Right,” I agreed. But secretly, I thought, “Why not? It’s not going anywhere.” I’ve
Tofacitinib in Amyopathic Dermatomyositis–Associated Interstitial Lung Disease
To the Editor: Anti–melanoma differentiation–associated protein (MDA) 5 (anti-MDA5)–positive amyopathic dermatomyositis (ADM)–associated interstitial lung disease (ILD) (hereafter, ADM-ILD) is a rapidly progressive and life-threatening disease. Despite aggressive conventional treatments with…
The DNA Repair Nuclease MRE11A Functions as a Mitochondrial Protector and Prevents T Cell Pyroptosis and Tissue Inflammation
In rheumatoid arthritis, T cells are deficient in the DNA repair nuclease MRE11A and age prematurely. Li et al. show that MRE11A is necessary to sustain mitochondrial fitness and ATP production. T cells deficient in MRE11A leak mtDNA into the cytoplasm, triggering pyroptosis
Mucosal Neuromas
Figure 1.
Sodium-Intake Reduction and the Food Industry
A recent report from the National Academies of Sciences, Engineering, and Medicine (NASEM) on dietary sodium intake adds overwhelming weight to the already strong imperative to reduce the amount of sodium in the U.S. food supply. Some food companies had
Sodium-Intake Reduction and the Food Industry
A recent report from the National Academies of Sciences, Engineering, and Medicine (NASEM) on dietary sodium intake adds overwhelming weight to the already strong imperative to reduce the amount of sodium in the U.S. food supply. Some food companies had
HIV-1 Epidemic Control — Insights from Test-and-Treat Trials
Debate ensued when mathematical models predicted that universal testing and treatment could achieve epidemic control within a few years in a high-burden setting. However, the idea rapidly gained new credence when antiretroviral therapy (ART)–induced viral suppression was shown to be
Case 22-2019: A 65-Year-Old Woman with Weakness, Dark Urine, and Dysphagia
Presentation of Case. Dr. Doll L. Golden (Medicine): A 65-year-old woman was admitted to this hospital because of falls, weakness, dark urine, and difficulty swallowing. Approximately 35 years before the current admission, the patient underwent staged male-to-female sex reassignment surgery
Persistent Gamma Spiking in SI Nonsensory Fast Spiking Cells Predicts Perceptual Success
Gamma oscillations are hypothesized to temporally coordinate sensory encoding. Shin and Moore found a distinct subtype of fast spiking interneurons (FS) in SI that are nonsensory responsive and spike regularly at gamma intervals. These “gamma regular nonsensory FS” could potentially
Case 22-2019: A 65-Year-Old Woman with Weakness, Dark Urine, and Dysphagia
Presentation of Case. Dr. Doll L. Golden (Medicine): A 65-year-old woman was admitted to this hospital because of falls, weakness, dark urine, and difficulty swallowing. Approximately 35 years before the current admission, the patient underwent staged male-to-female sex reassignment surgery
Mucosal Neuromas
Figure 1.
[Editorial] Smorgasbord or Smaug’s hoard?
Privacy with respect to personal information is generally regarded as a good thing, at least among those who came of age before Facebook. In May, 2018, the General Data Protection Regulation (GDPR) was enacted in the European Union, and the
An Integrative Model of Cellular States, Plasticity, and Genetics for Glioblastoma
Single-cell analyses of glioblastoma samples reveal multiple cellular states, their plasticity and the genetic underpinnings of state proportions in a given tumor.
[Editorial] Prioritising disability in universal health coverage
Current health systems are failing the 1 billion people worldwide living with disabilities. Unless access to health care is dramatically improved for this marginalised group, the goal of universal health coverage will not be achieved. These are the stark conclusions
Tofacitinib in Amyopathic Dermatomyositis–Associated Interstitial Lung Disease
To the Editor: Anti–melanoma differentiation–associated protein (MDA) 5 (anti-MDA5)–positive amyopathic dermatomyositis (ADM)–associated interstitial lung disease (ILD) (hereafter, ADM-ILD) is a rapidly progressive and life-threatening disease. Despite aggressive conventional treatments with…
Tofacitinib in Amyopathic Dermatomyositis–Associated Interstitial Lung Disease
To the Editor: Anti–melanoma differentiation–associated protein (MDA) 5 (anti-MDA5)–positive amyopathic dermatomyositis (ADM)–associated interstitial lung disease (ILD) (hereafter, ADM-ILD) is a rapidly progressive and life-threatening disease. Despite aggressive conventional treatments with…
Standards for Online and Remote Providers of Sexual and Reproductive Health Services
BASHH/FRSH standards are used by commissioners/CCGs and National Health Service (NHS) England to commission Sexual and Reproductive Health services in England and inform commissioning decisions in the devolved nations. The FRSH/BASHH Standards for Online and Remote Providers of Sexual and
Circular PVT1: an oncogenic non-coding RNA with emerging clinical importance
The importance of circular RNAs (circRNAs) in pathological processes like cancer is evident. Among the circRNAs, recent studies have brought circPVT1 under focus as the most potent oncogenic non-coding RNA. Recent studies on various aspects of circPVT1, including its biogenesis,
Prostate cancer tool may help patients to decide on treatment
Highlights from this issue
Reducing repeat emergency department attendance for non-urgent care: a systematic review of the effectiveness of interventions Paediatric Emergency medicine continues to evolve as a specialty around the world and with it, an increasing demand on those services, in the emergency
Seven days in medicine: 10-16 July 2019
Clinical negligenceNHS pay-outs of £2.4bn prompt call for reformMedical defence experts urged the UK government to hasten reform of the legal process for clinical negligence claims, as figures showed…
Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer
Several randomized trials have established the benefits of adding docetaxel or abiraterone to testosterone suppression in men with metastatic, hormone-sensitive prostate cancer. The survival benefits associated with docetaxel early in the course of treatment, particularly in men with high-volume…
Phenotype in an Infant with SOD1 Homozygous Truncating Mutation
To the Editor: Superoxide dismutase-1 (SOD1) is a ubiquitously expressed antioxidant enzyme. Mutations in SOD1 are associated with dominantly inherited amyotrophic lateral sclerosis, probably caused by the toxic effects of the protein rather than by loss of enzymatic activity. Here
Nintedanib for Systemic Sclerosis–Associated Interstitial Lung Disease
Systemic sclerosis is a rare and heterogeneous autoimmune disease characterized by immune dysregulation, microvascular damage, and organ fibrosis. Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis that tends to occur early in the course of disease; the
Vaccination over Parental Objection — Should Adolescents Be Allowed to Consent to Receiving Vaccines?
The United States has been experiencing an increasing number of measles outbreaks, and more measles cases were reported in the first 5 months of 2019 than in any full year since 1992, which was 8 years before endemic transmission was
Primary Care First — Is It a Step Back?
Evidence of the value of primary care to the U.S. health care system continues to grow. Supporting primary care is a major goal of the Centers for Medicare and Medicaid Services (CMS), which has added new billing codes to pay
Phenotype in an Infant with SOD1 Homozygous Truncating Mutation
To the Editor: Superoxide dismutase-1 (SOD1) is a ubiquitously expressed antioxidant enzyme. Mutations in SOD1 are associated with dominantly inherited amyotrophic lateral sclerosis, probably caused by the toxic effects of the protein rather than by loss of enzymatic activity. Here
COPD Exacerbations — A Target for Antibiotic Stewardship
Patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) in whom outpatient treatment fails are at risk for serious decompensation and hospitalization. Thus, when outpatients with COPD present with acutely worsening symptoms, clinicians are tempted to err on the
The recovery model and patient generated outcome measures
Robertson discusses the notions of cure and wellness.1 In mental health, the vision of healing as “thriving within one’s life as it is” is embedded in the recovery model. We always aim to reduce…
Vastus medialis obliquus (VMO) retraining or graduated loading programme for patellofemoral pain: different paradigm with similar results?
Our early research identified imbalance in vasti activation in people with patellofemoral pain (PFP) and that vasti retraining programmes could restore motor control and improve outcomes.1 2 For around a decade, many patients benefitted from this research and its translation
Strengths, weaknesses, opportunities and threats (SWOT) analysis of reinitiation into methamphetamine abusers: qualitative findings from an exploration of methamphetamine abusers in Shanghai, China
Background Despite high relapse rate among methamphetamine (MA) abusers, there still have been little empirical data to date detecting the risk factors related to craving and relapse from the perspective of MA abusers. Therefore, the aim of this study was
Targeting prognostic proinflammatory biomarkers to improve outcome on IO drugs
Continuing to improve outcomes of men with metastatic prostate cancer
Nature Reviews Clinical Oncology, Published online: 16 July 2019; doi:10.1038/s41571-019-0254-9 In the TITAN and ENZAMET trials, unprecedented overall survival outcomes were observed in patients with metastatic castration-sensitive prostate cancer receiving an agent targeting the androgen receptor in addition to androgen-deprivation
Hemolytic Transfusion Reactions
Blood transfusion is the most common therapeutic procedure performed in hospitalized patients; some 15% of inpatients receive blood components during their stay. Approximately 1% of transfused products result in serious adverse reactions, including hemolytic transfusion reactions, which account for…
The use of a hybrid mannequin for the modern high-fidelity simulation in the labor ward: The Italian experience of the EGEO group
Regular training in the management of intrapartum emergencies has been demonstrated to yield measurable benefits in terms of maternal and perinatal outcomes. Thanks to technologic advances,computerized full-body mannequins have been created and made available for high-fidelity simulation in obstetrics. The
Getting dynamic with eQTLs
Nature Reviews Genetics, Published online: 16 July 2019; doi:10.1038/s41576-019-0163-x A recent study in Science demonstrates how capturing gene expression over a developmental time course enables the discovery of dynamic expression quantitative trait loci (eQTLs) that would otherwise be challenging to
[Editorial] Baby foods: time to get tough on sugars
Childhood obesity is now one of the most challenging public health crises of our time, affecting low-income, middle-income, and high-income countries alike. According to WHO, in 2016, globally 41 million children younger than 5 years and 340 million children and
Identification of a Spinal Circuit for Mechanical and Persistent Spontaneous Itch
Pan et al. identify a microcircuit in the dorsal spinal cord that transmit mechanically evoked itch. Sensitization of this pathway is required for chronic itch development.
Reducing Cervical Cancer Deaths
A combination of increased cervical cancer screening, better coverage with the human papillomavirus (HPV) vaccine, and better access to radiotherapy will be needed to cut global cervical cancer incidence and deaths, according to a pair of studies in The Lancet
GP academic is suspended for six months after misleading employers about outside work
A professor of general practice who misled his employers at Warwick Medical School about his outside work and earnings has been suspended from the UK medical register for six months.When Robert…
Immune-checkpoint inhibition as first-line therapy for Hodgkin lymphoma
Nature Reviews Clinical Oncology, Published online: 15 July 2019; doi:10.1038/s41571-019-0255-8 The addition of the immune-checkpoint inhibitor nivolumab to first-line therapy with doxorubicin, vinblastine and dacarbazine seems feasible, with no signals of severe additional toxicities emerging. The high response rates and
Evaluating the Discordant Relationship Between Tarlov Cysts and Symptoms of Pudendal Neuralgia
Pudendal neuralgia is a painful neuropathic condition involving the pudendal nerve dermatome. Tarlov cysts have been reported in the literature as another potential cause of chronic lumbosacral and pelvic pain. Notably, they are often located in the distribution of the
Highly rearranged chromosomes reveal uncoupling between genome topology and gene expression
Nature Genetics, Published online: 15 July 2019; doi:10.1038/s41588-019-0462-3 Systematic analysis of highly rearranged balancer chromosomes in Drosophila shows that extensive changes to chromatin topology affect the expression of only a subset of genes.
Overvaluing individual consent ignores risks to tribal participants
Nature Reviews Genetics, Published online: 15 July 2019; doi:10.1038/s41576-019-0161-z Genomic studies often rely on individual-based consent approaches for tribal members residing outside of their communities. Tsosie et al. argue that this consent model fails to acknowledge the risks to small
Bayesian Computation through Cortical Latent Dynamics
Sohn et al. found that prior beliefs warp neural representations in the frontal cortex. This warping provides a substrate for the optimal integration of prior beliefs with sensory evidence during sensorimotor behavior.
UK firm pays $1.4bn to settle US allegations over opioid marketing
The UK conglomerate Reckitt Benckiser, maker of Durex and Lysol, will pay $1.4bn (£1.1bn; €1.2bn) to resolve civil litigation and criminal investigations launched by the US government over its…
Heartbeat: pacer risk in patients with right bundle branch block
A common question from primary providers is whether an ECG showing a right or left bundle branch block (RBBB or LBBB) is a cause for concern. Rasmussen et al1 estimated HRs and absolute risk of cardiovascular (CV) outcomes in over 200
Highlights from this issue
This month one member of the Triumvirate spends his sabbatical in Australia and we welcome Brisbane-based Claire Wainwright as our new deputy editor of Thorax. What better opportunity to celebrate all things antipodean with a “Down Under” edition of Airwaves?
The Thrombosis Research Institute, London
The past, present, and future of global clinical research into thrombosis and anticoagulation at the TRI London are discussed
Planned vaginal delivery and cardiovascular morbidity in pregnant women with heart disease
Though consensus guidelines on the management of cardiovascular disease (CVD) in pregnancy reserve cesarean delivery for obstetric indications, there is a paucity of data to support this approach.
C-Reactive Protein Testing to Guide Antibiotic Prescribing for COPD Exacerbations
Primary care providers are responsible for the majority of antibiotic prescriptions, and the highest overall number of such prescriptions are issued by family physicians. There is reason to believe that many of these prescriptions could be avoided. Unwarranted use of
Incorporating the Probability of Competing Event(s) into the Preeclampsia Competing Risk Algorithm
The potential of genomics for restoring ecosystems and biodiversity
Nature Reviews Genetics, Published online: 12 July 2019; doi:10.1038/s41576-019-0152-0 Earth’s landscapes and biodiversity are being eroded at an unprecedented pace and scale. This Review argues that genomics tools need to be adopted in restoration ecology to help reverse the environmental
Does stress echocardiography add incremental value to baseline ejection fraction for the early identification of candidates for implantable defibrillators?
Objective A reduction in left ventricular ejection fraction (EF) remains the strongest indicator of increased risk of sudden cardiac death after an acute myocardial infarction (AMI). Guidelines recommend that patients with an EF ≤35%, 6–12 weeks after AMI should be
Case 20-2019: A 52-Year-Old Woman with Fever and Rash after Heart Transplantation
Presentation of Case. Dr. Taylor A. Lebeis: A 52-year-old woman who had undergone orthotopic heart transplantation because of dilated cardiomyopathy was admitted to this hospital with painful red lesions on the left arm and leg. Eight years before this admission,
C-Reactive Protein Testing to Guide Antibiotic Prescribing for COPD Exacerbations
Primary care providers are responsible for the majority of antibiotic prescriptions, and the highest overall number of such prescriptions are issued by family physicians. There is reason to believe that many of these prescriptions could be avoided. Unwarranted use of
Hemolytic Transfusion Reactions
Blood transfusion is the most common therapeutic procedure performed in hospitalized patients; some 15% of inpatients receive blood components during their stay. Approximately 1% of transfused products result in serious adverse reactions, including hemolytic transfusion reactions, which account for…
Mortality and cancer incidence among underground uranium miners in the Czech Republic 1977-1992
Objectives Uranium miners in Příbram, Czech Republic were exposed to low and moderate levels of radon gas and other hazards. It is unknown whether these hazards increase the risk of mortality or cancer incidence when compared with the general Czech
Patients to be asked what they need from doctors
The government has instructed Health Education England to consult patients and the public on what they need from “21st century” medical graduates.The requirement is set out in the Department of…
Postpartum psychosis in a non-native language-speaking patient: A perspective on language barriers and cultural competency
Postpartum psychosis is a condition characterised by rapid onset of psychotic symptoms several weeks after childbirth. Outside of its timing and descriptions of psychotic features, minimal research exists due to its relative rarity (1 to 2 per 1000 births in
The era of alternative designs to connect randomized clinical trials and real-world data
Nature Reviews Clinical Oncology, Published online: 11 July 2019; doi:10.1038/s41571-019-0250-0 The era of alternative designs to connect randomized clinical trials and real-world data
Generation of Human PSC-Derived Kidney Organoids with Patterned Nephron Segments and a De Novo Vascular Network
Human PSC-derived organoids are an amenable platform for understanding human development and diseases despite numerous limitations. Low et al. establish a versatile platform for generating vascularized and patterned kidney organoids. Using this platform, they identified a non-conventional origin of renal vasculature
Mechanisms of Progression of Myeloid Preleukemia to Transformed Myeloid Leukemia in Children with Down Syndrome
Myeloid leukemia in Down syndrome (ML-DS) evolves from transient abnormal myelopoiesis (TAM). Labuhn et al. show that trisomy 21 and GATA1 mutations are sufficient for the development of TAM. They further identify and functionally validate additional variants that drive TAM to
Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer
Several randomized trials have established the benefits of adding docetaxel or abiraterone to testosterone suppression in men with metastatic, hormone-sensitive prostate cancer. The survival benefits associated with docetaxel early in the course of treatment, particularly in men with high-volume…
Greater support and resources needed for cancer survivors returning to work
Thyroid Function and Conception
This clinical scenario of a young, healthy woman who is found to have a serum thyrotropin concentration in the mid-to-upper reference range for nonpregnant women, a normal free T4 concentration, and a positive thyroid antibody titer is a common clinical
Plasma Cells Are Obligate Effectors of Enhanced Myelopoiesis in Aging Bone Marrow
Pioli et al. demonstrate that bone marrow plasma cells (PCs) increase in number with age and play an obligate role in the increased production of myeloid cells during aging. They further demonstrate that old PCs are a source of myelopoietic cytokines
Hemolytic Transfusion Reactions
Blood transfusion is the most common therapeutic procedure performed in hospitalized patients; some 15% of inpatients receive blood components during their stay. Approximately 1% of transfused products result in serious adverse reactions, including hemolytic transfusion reactions, which account for…
“Double Tongue” Appearance in Ludwig’s Angina
Figure 1.
Oncogene Amplification in Growth Factor Signaling Pathways Renders Cancers Dependent on Membrane Lipid Remodeling
Persistent growth factor receptor signaling and metabolic reprograming are hallmarks of cancer. Bi et al. show that LPCAT1-mediated phospholipid remodeling supports the sustained oncogenic activity of growth factor receptors on plasma membrane of tumor cells, suggesting an actionable dependency in a
Thyroid Function and Conception
This clinical scenario of a young, healthy woman who is found to have a serum thyrotropin concentration in the mid-to-upper reference range for nonpregnant women, a normal free T4 concentration, and a positive thyroid antibody titer is a common clinical
Vaccination over Parental Objection — Should Adolescents Be Allowed to Consent to Receiving Vaccines?
The United States has been experiencing an increasing number of measles outbreaks, and more measles cases were reported in the first 5 months of 2019 than in any full year since 1992, which was 8 years before endemic transmission was
Vaccination over Parental Objection — Should Adolescents Be Allowed to Consent to Receiving Vaccines?
The United States has been experiencing an increasing number of measles outbreaks, and more measles cases were reported in the first 5 months of 2019 than in any full year since 1992, which was 8 years before endemic transmission was
A Single-Cell Transcriptomic Atlas of Human Neocortical Development during Mid-gestation
An extensive single-cell catalog of cell types in the mid-gestation human neocortex extends our understanding of early cortical development, including subplate neuron transcriptomes, cell-type-specific regulatory networks, brain evolution, and the cellular basis of neuropsychiatric disease.
Case 21-2019: A 31-Year-Old Woman with Vision Loss
Presentation of Case. Dr. Priya Srikanth (Neurology): A 31-year-old woman was evaluated in the emergency department of this hospital because of vision loss. Three weeks before presentation, blurry vision in the left eye developed gradually, with perception of distant objects
Vaccination over Parental Objection — Should Adolescents Be Allowed to Consent to Receiving Vaccines?
The United States has been experiencing an increasing number of measles outbreaks, and more measles cases were reported in the first 5 months of 2019 than in any full year since 1992, which was 8 years before endemic transmission was
Augmenting Immunotherapy Impact by Lowering Tumor TNF Cytotoxicity Threshold
New opportunities are needed to increase immune checkpoint blockade (ICB) impact for cancer patients. A genome-wide CRISPR/Cas9 screen uncovered several hits in the TNF pathway sensitizing tumor cells to T cell elimination. TNF antitumor activity was generally limited in tumors at
[Editorial] Physician burnout: a global crisis
Hui Wang, a 32-year-old Chinese ophthalmologist, experienced sudden cardiac death on June 30, after working with fever for 6 days in Beijing. Hui was the father of a 1-year-old girl, and married to a doctor, who donated Hui’s corneas to
Sister First, Doctor Second
“I think your brother has schizophrenia,” she said. I was entering my third year of medical school when I received a phone call from my brother’s friend. She shared enough detail to suggest that he had a brewing psychotic illness,
COPD Exacerbations — A Target for Antibiotic Stewardship
Patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) in whom outpatient treatment fails are at risk for serious decompensation and hospitalization. Thus, when outpatients with COPD present with acutely worsening symptoms, clinicians are tempted to err on the
Highlights from this issue
Neurologists are keen to remind their trainees that ‘it’s all in the history’. An illness’s time course is a particularly important part of the history, providing the time signature for the underlying pathological process and thus significantly narrowing the differential
Perinatal care: mental health support expands but weight and smoking services “extremely disappointing”
There has been significant expansion in mental health support for women during pregnancy and postnatally, according to the latest snapshot survey of NHS maternity and neonatal services in England,…
Corticolimbic fast-tracking in functional neurological disorders: towards understanding of the ‘dynamic lesion of Jean-Martin Charcot
Have we found the ‘dynamic lesion’ of Jean-Martin Charcot in functional neurological disorders? At the end of the 19th century, hysterical symptoms were regarded by one of the founders of modern neurology, Jean-Martin Charcot, as manifestations of a ‘dynamic lesion’
‘Not all drugs (and route) are same
I read with great interest, study by French vasculitis group, the MAINRITSAN 2 trial.1 The results of this trial again underline our limitations for search of biomarker, which can predict relapse of antineutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitis. I have few concerns about
A Most Reckless Proposal — A Plan to Continue Asbestos Use in the United States
Each year, nearly 40,000 Americans die often painful, protracted deaths from diseases caused by asbestos. These deaths occur in firefighters, police officers, construction workers, miners, military veterans, shipyard workers, and maintenance workers whose exposures to asbestos are primarily…
DNA as a biological lens
Nature Reviews Genetics, Published online: 10 July 2019; doi:10.1038/s41576-019-0157-8 New research in Cell describes the technique of ‘DNA microscopy’, in which the spatial distribution of mRNAs is inferred through sequencing DNA tags, without direct visualization.
Chronic Rhinosinusitis with Nasal Polyps
Foreword. This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author’s clinical recommendations. Stage.
Faulty devices: how does cardiology compare to aviation?
Comparing the investigative process that occurs in the aviation world after a disaster with what, if any, occurs in cardiology after device failures or human errors
Nintedanib for Systemic Sclerosis–Associated Interstitial Lung Disease
Systemic sclerosis is a rare and heterogeneous autoimmune disease characterized by immune dysregulation, microvascular damage, and organ fibrosis. Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis that tends to occur early in the course of disease; the
A Most Reckless Proposal — A Plan to Continue Asbestos Use in the United States
Each year, nearly 40,000 Americans die often painful, protracted deaths from diseases caused by asbestos. These deaths occur in firefighters, police officers, construction workers, miners, military veterans, shipyard workers, and maintenance workers whose exposures to asbestos are primarily…
TREM2 Acts Downstream of CD33 in Modulating Microglial Pathology in Alzheimer’s Disease
Microglial receptors CD33 and TREM2 exhibit opposite effects on Aβ pathology and microglial activity in AD mice. In crosstalk between these receptors, TREM2 is required for differential gene expression in 5xFAD mice deficient for CD33 and acts downstream of CD33.
[Editorial] A plan for fragile X syndrome with wide-ranging consequences
The most common inherited cause of intellectual and developmental disability worldwide is fragile X syndrome, caused by a mutation in the FMR1 gene on the X chromosome. To accelerate the development of effective interventions to prevent or treat fragile X
[Editorial] Albinism: myths and reality
The establishment of June 13 as International Albinism Awareness Day by the UN General Assembly “as a response to the appeal by civil society organizations that advocate for individuals with albinism as a specific group with specific needs that require
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